chr8-19966981-T-C

Variant names:

• chr8-19966981-T-C
• rs13702
• NM_000237.3:c.*1671T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000237.3(LPL):​c.*1671T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 152,466 control chromosomes in the GnomAD database, including 10,325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (10304 hom., cov: 33)
  • Exomes 𝑓: 0.27 (21 hom.)
• Consequence: LPL NM_000237.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4 O:1
• Conservation: PhyloP100: -1.17
• Publications: 130 publications found

Genes affected

LPL (HGNC:6677): (lipoprotein lipase) LPL encodes lipoprotein lipase, which is expressed in heart, muscle, and adipose tissue. LPL functions as a homodimer, and has the dual functions of triglyceride hydrolase and ligand/bridging factor for receptor-mediated lipoprotein uptake. Severe mutations that cause LPL deficiency result in type I hyperlipoproteinemia, while less extreme mutations in LPL are linked to many disorders of lipoprotein metabolism. [provided by RefSeq, Jul 2008]

LPL Gene-Disease associations (from GenCC):

• familial lipoprotein lipase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Laboratory for Molecular Medicine, Ambry Genetics
• hyperlipidemia, familial combined, LPL related

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 8-19966981-T-C is Benign according to our data. Variant chr8-19966981-T-C is described in ClinVar as Benign. ClinVar VariationId is 40131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000237.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPL	NM_000237.3	MANE Select	c.*1671T>C		3_prime_UTR	Exon 10 of 10	NP_000228.1	P06858

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPL	ENST00000650287.1	MANE Select	c.*1671T>C		3_prime_UTR	Exon 10 of 10	ENSP00000497642.1	P06858
	LPL	ENST00000965928.1		c.*1671T>C		3_prime_UTR	Exon 12 of 12	ENSP00000635987.1
	LPL	ENST00000965929.1		c.*1671T>C		3_prime_UTR	Exon 10 of 10	ENSP00000635988.1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53381 AN: 151912 Hom.: 10288 Cov.: 33

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.332

GnomAD4 exome AF: 0.273 AC: 119 AN: 436 Hom.: 21 Cov.: 0 AF XY: 0.252 AC XY: 66 AN XY: 262

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.273 AC: 117 AN: 428

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.352 AC: 53441 AN: 152030 Hom.: 10304 Cov.: 33 AF XY: 0.347 AC XY: 25766 AN XY: 74302

African (AFR) AF: 0.513 AC: 21258 AN: 41436

American (AMR) AF: 0.298 AC: 4559 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1512 AN: 3464

East Asian (EAS) AF: 0.205 AC: 1061 AN: 5180

South Asian (SAS) AF: 0.243 AC: 1172 AN: 4820

European-Finnish (FIN) AF: 0.260 AC: 2744 AN: 10574

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19932 AN: 67962

Other (OTH) AF: 0.332 AC: 699 AN: 2106

Alfa AF: 0.313 Hom.: 30349

Bravo AF: 0.361

Asia WGS AF: 0.256 AC: 892 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Hyperlipoproteinemia, type I (1)
-	-	-	High density lipoprotein cholesterol level quantitative trait locus 11 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.56
DANN	Benign	0.65
PhyloP100		-1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13702; hg19: chr8-19824492; COSMIC: COSV60931277;